Asthma

Chronic inflammatory disease of the airways associated with airway hyperresponsiveness leading to recurrent episodes of wheezing, breathlessness, chest tightness and/or coughing that can vary over time and in intensity.

• M/C chronic disease of childhood

History:

The modern concept of asthma as an immunologic disorder has its foundations in clinical observations spanning two centuries. This included early descriptions of “asthmatic sputum” associated with specific cell types, Charcot–Leyden crystals, and Curshmann spirals, inflammation of smaller airways, and paroxysms induced by environmental exposures. In the early 1920s, specific mechanisms for allergic diseases including asthma, allergic rhinitis, and atopic dermatitis were identified to be mediated by serum substances known as reagins. This was first exemplified by the passive transfer of fish hypersensitivity from one individual to another. Carl Prausnitz observed that his colleague Hans Küstner was exceptionally sensitive to cooked fish. To determine if this sensitivity was due to serum factors, he self-administered an intradermal injection of serum from his colleague and subsequently developed a new hypersensitivity to fish at the site of injection. Subsequently, it was shown that this transfer of skin sensitization, the Prausnitz–Küstner reaction, was mediated by a newly identified antibody class, IgE, which mediated hypersensitivity reactions to a wide range of allergens in multiple tissues including the lung. Today, approximately 60 % of asthma is linked to IgE-mediated reactions, and IgE remains one of the best predictors for the development of allergic asthma in humans. Further unpacking of these initial key discoveries has informed our modern understanding of asthma immunology and the importance of IgE in this process.

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Epidemiology

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Etiology

Asthma subphenotypes:

Acute exacerbation triggers:

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Pathophysiology

Airway pathology:

Intermittent and reversible airway obstruction, chronic bronchial inflammation with eosinophils, bronchial smooth muscle hypertrophy and hyperreactivity, and increased mucus secretion.

1. Bronchoconstriction (dominant physiological event):
2. Airway edema
3. Airway hyperresponsiveness
4. Airway remodeling

Histopathology:

• Mucous plugs contain,
  • Curschmann spirals (whorls of shred epithelium)
  • Charcot-Leyden crystals (crystalloids made of eosinophil proteins)

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Presentation

Acute exacerbation of asthma:

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Diagnosis

Bronchial (methacholine/histamine) challenge test:

Bronchoprovocation test where patient breathes in nebulized methacholine (M3)/histamine (H1) to provoke bronchoconstriction.

Spirometry:

• FEV1 < 80%
• FVC
• FEV1/FVC < 0.7
• FEV25-75

Allergy test:

• Skin test
• RAST (Radio-allergo-sorbent allergen-specific IgE)

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Management

O-SHIT!

• Oxygen
• Salbutamol
• Hydrocortisone
• Ipratropium
• Theophylline

Bronchodilators:

• Beta-2 sympathomimetics: Salbutamol, Terbutaline, Salmeterol, Formoterol
• Methylxanthines: Theophylline, Aminophylline
• Anticholinergics: Ipratropium bromide, Tiotropium bromide

Anti-inflammatory:

• Corticosteroids (Inhalational): Beclomethasone, Budesonide, Fluticasone
• Corticosteroids (Systemic): Prednisolone, Hydrocortisone
• Mast cell stabilizers: Sodium cromoglycate, Ketotifen
• Leukotriene antagonists: Montelukast, Zafirlukast
  • Block LT1-receptors → ↓ eosinophilic inflammation → Bronchodilation

Novel drugs:

• Monoclonal antibody against IgE: Omalizumab
• Monoclonal anti–IL-5 antibodies: Mepolizumab, Benralizumab
• Recombinant soluble interleukin (IL)-4 receptor antagonists: Dupilumab

Acute exacerbation of asthma:

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Summary